Charles G. Hoogstraten Research Interests continued
A second major focus is the protein-RNA recognition events that are important in the regulation of alternative pre-mRNA splicing in eukaryotes. Alternative splicing is emerging as a major contributor to the regulation of gene expression, and also plays a dominant role in generating diversity in the proteome, which can exceed the diversity of the genome by orders of magnitude. Sequences in the pre-mRNA exons and introns can either favor or disfavor the usage of nearby splice sites when recognized by modular RNA-binding proteins of the SR family. SR proteins are modular molecules whose RNA-binding affinity and specificity emerge in a nonlinear way from the characteristics of individual RNA-binding domains. We will use a combination of NMR studies of domain orientation and ligand-induced folding, EPR in combination with site-directed spin labeling for studies of global interdomain structure, and solution thermodynamics using isothermal titration calorimetry (ITC) to unravel the physicochemical bases of this key RNA-protein recognition event.